Two different mechanisms have been proposed by which dopamine and dobutamine cause negative interference for tests that use peroxidase-catalyzed oxidation of hydrogen peroxide for the generation of chromophores. We further investigated the mechanism of inhibition with dopamine, dobutamine, and structurally related compounds (L-dopa, L-methyldopa, and tyramine) on peroxidase-catalyzed reaction(s) for uric acid, creatinine, total cholesterol, and glycerol-blanked triglycerides. Pretreatment of samples with benzene-boronic acid (in up to 6 times excess of drug concentration) had no effect on the inhibition of the reactions. Spectrophotometric studies indicated that increasing peroxide concentration in the absence of drug or in the presence of a constant drug concentration initially increases then decreases absorbances. At a constant peroxide concentration, increasing drug concentration increased the absorbance. The products of the peroxidase-catalyzed reaction were stable. The complexity of interference with these drugs requires additional studies.